Retinitis pigmentosa (RP) is one of the most frequently occurring blinding retinal dystrophies and is characterized not only by the loss of rod function but also by cone system abnormalities as well. This research proposal is focussed on foveal contrast perception in RP: the origin of contrast processing deficits and their impact on foveal visual function. Parallel investigations of normal control subjects will better define mechanisms of contrast processing in visually normal individuals. The specific aims are: (1) to test particular hypotheses concerning the loss of foveal spatial vision in RP (hypothesis 1: selective loss of input to high spatial frequency mechanisms; hypothesis 2: altered foveal spatial grain; hypothesis 3: reduced contrast gain); (2) to determine the relationship between intraocular light scatter, posterior subcapsular lens opacities. disability glare, and foveal visual function in patients with RP and related photoreceptor degenerations; (3) to define the relative contributions of linear and nonlinear mechanisms to spatial and temporal contrast sensitivity in RP patients and in visually normal individuals; and (4) to test the hypothesis that contrast thresholds for letter identification are mediated by the same visual mechanism as contrast thresholds for the detection of sinusoidal gratings. These aims will be accomplished by a series of interrelated psychophysical investigations of foveal vision loss in a cohort of approximately 1,000 well-categorized patients with RP, many with identified mutations in the genes involved in rod phototransduction, available through the University of Illinois Research Center of the National Retinitis Pigmentosa Foundation Fighting Blindness. The results of these studies are intended to lead to clinically applicable methods that will allow an earlier detection of foveal vision loss in RP patients, to a more precise characterization of foveal visual impairment in individual patients, to the optimization of strategies for visual rehabilitation, and to a more sensitive evaluation of potential methods for therapeutic intervention.